Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment

Linfoma cutaneo epiteliotropo: aspetti clinico-patologici in 20 cani

Canine epitheliotropic cutaneous lymphoma, also named mycosis fungoides, has been described as an uncommon cutaneous lymphoma of T-cell origin, which is histologically characterized by the epitheliotropism of neoplastic T-lymphocytes. Two variants have been reported in man, based upon clinical and histopathological features: classical mycosis fungoides and Sezary syndrome. The disease in dogs is clinically classified as cutaneous nodular form, exfoliative erythroderma, mucocutaneous form, and oral form. Aim of the study - The aim is to point out the most interesting clinical and histopathological findings for the diagnosis, also carrying out a comparison with the human species. Material and methods - We report the cases of 20 dogs, diagnosed with epitheliotropic cutaneous lymphoma. Medical records of these animals were reviewed for rilevant data on signalment, anamnesis, clinical examination and histopathologic diagnosis. Results - All the clinical variants described by Scott in veterinary medicine were present alone or in combination: exfoliative erythroderma (75% dogs), mucocutaneous form (65% dogs), cutaneous nodular form (55% dogs), and oral form (25% dogs). On the basis of histological features, the most represented variant was pagetoid reticulosis (14/20 dogs, 70%). Sezary syndrome could not be found. Discussion - The clinical and histopathological features that were observed reflected those previously reported in the published literature, and showed interesting findings to be compared with the homologous human neoplasia

Selective augmentation of stem cell populations in structural fat grafts for maxillofacial surgery.

Structural fat grafting utilizes the centrifugation of liposuction aspirates to create a graded density of adipose tissue. This study was performed to qualitatively investigate the effects of centrifugation on stem cells present in adipose tissue. Liposuction aspirates were obtained from healthy donors and either not centrifuged or centrifuged at 1,800 rpm for 3 minutes. The obtained fat volumes were divided into three layers and then analyzed. The results demonstrate that centrifugation induces a different distribution of stem cells in the three layers. The high-density layer displays the highest expression of mesenchymal stem cell and endothelial markers. The low-density layer exhibits an enrichment of multipotent stem cells. We conclude that appropriate centrifugation concentrates stem cells. This finding may influence the clinical practice of liposuction aspirate centrifugation and enhance graft uptake

Anagrelide treatment and cardiovascular monitoring in essential thrombocythemia. A prospective observational study

In this prospective observational single-center study, 55 patients with essential thrombocythemia who were candidates for second line treatment with anagrelide (ANA) received a preliminary cardiovascular (CV) clinical, instrumental and biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure, heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in-depth CV screening, 54 out of 55 patients were deemed to be fit for ANA treatment. Thirty-eight of the 55 patients received ANA treatment for a median of 36 months (range 3-48), and were monitored using the same CV evaluation. Fourteen of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2 arterial hypertension, 2 acute myocardial infarction) that were not predicted by the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non-cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did not appear to be necessary in ET patients to evaluate their suitability for ANA treatment, and, moreover, was not able to predict the occurrence of CV adverse events during ANA treatment. Nevertheless, the CV adverse events (mostly palpitations and edema) were easily managed by the hematologists, and required the cardiologist involvement in very few selected cases

Gene expression profile of mesenchymal stem cell-specific markers.

<p>Gene expression profile of mesenchymal stem cell-specific markers in the LDL (white bars), MDL (grey bars), and HDL (black bars). The results are reported as ratios (R) with respect to the mRNA expression levels of non-centrifuged fat (not shown).</p

Gene expression profile of genes associated with mesenchymal stem cell markers.

<p>Gene expression profile of genes associated with mesenchymal stem cell markers in the LDL (white bars), MDL (grey bars), and HDL (black bars). The results are reported as ratios (R) with respect to the mRNA expression levels of non-centrifuged fat (not shown).</p

List of genes analyzed by real-time PCR.

<p>List of genes analyzed by real-time PCR.</p

Gene expression profile of stemness markers.

<p>Gene expression profile of stemness markers in the LDL (white bars), MDL (grey bars), and HDL (black bars). The results are reported as ratios (R) with respect to the mRNA expression levels of non-centrifuged fat (not shown).</p

Commitment ability of stem cells present in the HDL.

<p>(A) Osteogenic commitment. Immunofluorescence confirms positive staining for osteonectin (red) in both 2D cultures (scale bar = 20 µm) and 3D cultures (scale bar = 50 µm). Real-time PCR detects the expression of osteopontin (OPN), osteonectin (ON), osteocalcin (OCN), and type I collagen (COL1A1), which are typical markers of osteogenic commitment. (B) Adipogenic commitment. ORO staining confirms lipid deposition inside the cytoplasm (red) in 2D cultures (scale bar = 50 µm). SEM analysis of 3D cultures reveals the typical adipogenic round shape of cells (scale bar = 10 µm). Genes related to the adipogenic phenotype, such as PPARG, LPL, GLUT4, and ADIPOQ, are expressed. (C) Chondrogenic commitment. In the 3D cultures, the cells are organized into their typical clusters, as shown by SEM analysis (scale bar = 50 µm), and only express type II collagen (COL2A1), as detected by real-time PCR. (D) Neuronal commitment. Immunofluorescence confirms positive staining for TUBB3 (red) in both 2D cultures (scale bar = 40 µm) and 3D cultures (scale bar = 100 µm). High expression of TUBB3 and low expression of GFAP are evident. (E) Glial commitment. Immunofluorescence confirms positive staining for GFAP in both 2D cultures (red, scale bar = 20 µm) and 3D cultures (green, scale bar = 100 µm), where significant GFAP mRNA expression is also detectable. (F) Endothelial commitment. Immunofluorescence confirms positive staining for VWF (red) in 2D cultures (scale bar = 20 µm) and for CD31 (green) in 3D cultures (scale bar = 100 µm). In the 3D scaffolds, the cells are also able to organize into micro-capillary vessels. Gene expression of endothelial markers, such as CD31 and VEGF, is clearly detectable.</p